1. Field of the Invention
The invention relates to methods and apparatus for determining the concentration of a gas in a mixture.
2. Description of the Prior Art
Gas mixtures are routinely analyzed in fields ranging from medical diagnostics to automobile design. Techniques used vary widely and include mass spectroscopy, infrared spectroscopy, chemiluminescence and flame ionization. Regardless of the application, accuracy, reliability, convenient operation, low cost and preferably real-time analysis results are desirable. In the field of medical diagnostics, convenient, patient-friendly operation and real-time delivery of results are crucial for successful clinical implementation.
Currently available methods for determining the concentration of a gas in a mixture typically require use of a reference as in U.S. Pat. No. 5,640,014 to Sauke et al. wherein a reference signal or reference gas is used in a diode laser spectroscopy method to determine the isotopic ratio of a gas in a sample. Other methods involve deliberate introduction of a trace gas to the gas mixture to be analyzed as in U.S. Pat. No. 6,412,333 to Inoue et al. U.S. Pat. No. 6,412,333 describes an auto exhaust analyzer system and method wherein a trace gas is introduced into the exhaust gas stream, the mass of the trace gas is calculated using the analyzer and the calculated mass then compared with the known mass of trace gas to verify the accuracy of the analysis. Still other techniques compensate for inaccuracy in non-dispersive infrared analysis using signal processing techniques such as U.S. Pat. No. 5,464,983 to Wang which describes measurement of change of signal (CS) and change of change of signal (CCS) and comparison of CCS data obtained to CCS data for known gases at known concentrations and temperatures.
In the field of medical diagnostics, nitrogen monoxide (NO) is a well-established indicator of pulmonary function. Analysis of exhaled nitric oxide provides a health care provider with a non-invasive test for inflammatory diseases of the lower airways such as asthma. Widely used diagnostic tests for asthma such as spirometry give only limited and indirect information about lower airway inflammation. Current methods measuring exhaled NO for assessing lung function, such as U.S. Pat. No. 5,447,165 to Gustafsson, use mass spectroscopy and chemiluminescence to measure the time distribution of NO formed during exhalation and require that results be compared with unimpaired lung function of a living subject reference. U.S. Pat. No. 6,099,480 to Gustafsson describes collection of human breath and analysis for NO content using chemiluminescence or reagent-based chemical analysis techniques. U.S. Pat. No. 6,419,634 to Gaston et al. uses reagent-based calorimetric NO assay analysis of exhaled human breath condensate to evaluate airway inflammation.
Endogenous nitric oxide emanating from the airways and lungs is the preferred indicator of airway inflammation. Hence, breath collection techniques to collect this endogenous nitric oxide while excluding exhaled nasal NO from study have been developed. U.S. Pat. No. 6,010,459 to Silkoff et al. requires a patient to exhale at a constant rate and increases pressure in the mouth to close off the nasopharynx during exhalation thereby excluding nasal NO. U.S. Pat. No. 6,038,913 to Gustafsson et al. requires that a patient exhale against a back pressure during the later phase of an exhalation. U.S. Pat. No. 5,922,610 to Alving et al. describes a face mask that tightly covers the nose and/or mouth of the subject. Such techniques that require controlled exhalation by a patient can be difficult for those patients with impaired respiratory function and especially for pediatric patients. All of these methods require frequent calibration of the NO sensor using a calibration gas with a known NO concentration. This requirement complicates use of such sensing technology in a clinical setting.
Thus, there exists a need for accurately determining the concentration of a specific gas of interest in an as-obtained gas mixture sample without introduction of any additional reference gas. There exists further need for accurately assessing airway inflammation, using a single exhaled breath from a single patient without any healthy lung function reference. Preferably, such airway inflammation assessment is conveniently conducted in a clinical setting, maximizes patient comfort and provides real-time results that can enable a health care provider to diagnose and treat a patient in a single clinic visit